Association Between Medication-Taking and Refractive Error in a Large General Population-Based Cohort

Patasova, Karina; Khawaja, Anthony P; Tamraz, Bani; Williams, Katie; Mahroo, Omar A.; Freidin, Maxim B.; Solebo, Ameenat Lola; Vehof, Jelle; Falchi, Mario; Rahi, Jugnoo S; Hammond, Chris; Hysi, Pirro G.

doi:10.1167/iovs.62.2.15

Cited by 5 publications

(5 citation statements)

References 51 publications

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“…A causal role for particular medications in promoting RE was described long before MR research commenced [74]. For example, dorzolamide is a sulfonamide drug and was previously linked to transient myopia episodes [75,76], whereas the same conclusion was drawn from a recent MR study by Patasova et al [77]. Due to inevitable correlations between some medications and primary disease, Patasova et al used SNPs associated with primary diseases as IVs and their effects over spherical equivalent (SE) for the outcome and suggested a causal effect of multisite chronic pain over hyperopic RE 74.…”

Section: Re and Related Factorsmentioning

confidence: 92%

Mendelian randomization analyses in ocular disease: a powerful approach to causal inference with human genetic data

Liu

Huang

et al. 2022

J Transl Med

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Ophthalmic epidemiology is concerned with the prevalence, distribution and other factors relating to human eye disease. While observational studies cannot avoid confounding factors from interventions, human eye composition and structure are unique, thus, eye disease pathogenesis, which greatly impairs quality of life and visual health, remains to be fully explored. Notwithstanding, inheritance has had a vital role in ophthalmic disease. Mendelian randomization (MR) is an emerging method that uses genetic variations as instrumental variables (IVs) to avoid confounders and reverse causality issues; it reveals causal relationships between exposure and a range of eyes disorders. Thus far, many MR studies have identified potentially causal associations between lifestyles or biological exposures and eye diseases, thus providing opportunities for further mechanistic research, and interventional development. However, MR results/data must be interpreted based on comprehensive evidence, whereas MR applications in ophthalmic epidemiology have some limitations worth exploring. Here, we review key principles, assumptions and MR methods, summarise contemporary evidence from MR studies on eye disease and provide new ideas uncovering aetiology in ophthalmology.

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Section: Re and Related Factorsmentioning

confidence: 92%

Mendelian randomization analyses in ocular disease: a powerful approach to causal inference with human genetic data

Liu

Huang

et al. 2022

J Transl Med

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“…Recent MR studies suggested that higher IOP is associated with lower (more myopic) RE. Further, some genetic loci exhibited pleiotropic effects with VCDR, IOP, POAG, and myopia .…”

Section: Methodsmentioning

confidence: 99%

Association Between Myopic Refractive Error and Primary Open-Angle Glaucoma

et al. 2022

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IMPORTANCERefractive error (RE) is the most common form of visual impairment, and myopic RE is associated with an increased risk of primary open-angle glaucoma (POAG). Whether this association represents a causal role of RE in the etiology of POAG remains unknown.OBJECTIVE To evaluate shared genetic influences and investigate the association of myopic RE with the risk for POAG.DESIGN, SETTING, AND PARTICIPANTS Observational analyses were used to evaluate the association between mean spherical equivalent (MSE) RE (continuous trait) or myopia (binary trait) and POAG risk in individuals from the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort. To quantify genetic overlap, genome-wide genetic correlation analyses were performed using genome-wide association studies (GWAS) of MSE RE or myopia and POAG from GERA. Potential causal effects were assessed between MSE RE and POAG using 2-sample Mendelian randomization. Genetic variants associated with MSE RE were derived using GWAS summary statistics from a GWAS of RE conducted in 102 117 UK Biobank participants. For POAG, we used GWAS summary statistics from our previous GWAS (3836 POAG cases and 48 065 controls from GERA). Data analyses occurred between July 2020 and October 2021. MAIN OUTCOMES AND MEASURE Our main outcome was POAG risk as odds ratio (OR) caused by per-unit difference in MSE RE (in diopters).RESULTS Our observational analyses included data for 54 755 non-Hispanic White individuals (31 926 [58%] females and 22 829 [42%] males). Among 4047 individuals with POAG, mean (SD) age was 73.64 (9.20) years; mean (SD) age of the 50 708 controls was 65.38 (12.24) years. Individuals with POAG had a lower refractive MSE and were more likely to have myopia or high myopia compared with the control participants (40.2% vs 34.1%, P = 1.31 × 10 −11 for myopia; 8.5% vs 6.8%, P = .004 for high myopia). Our genetic correlation analyses demonstrated that POAG was genetically correlated with MSE RE (r g , −0.24; SE, 0.06; P = 3.90 × 10 −5 ), myopia (r g , 0.21; SE, 0.07; P = .004), and high myopia (r g , 0.23; SE, 0.09; P = .01). Genetically assessed refractive MSE was negatively associated with POAG risk (inverse-variance weighted model: OR per diopter more hyperopic MSE = 0.94; 95% CI, 0.89-0.99; P = .01). CONCLUSIONS AND RELEVANCEThese findings demonstrate a shared genetic basis and an association between myopic RE and POAG risk. This may support population POAG risk stratification and screening strategies, based on RE information.

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“… 53 Furthermore, a bidirectional relationship was found to exist between insomnia and CP 21 and between prescription opioid use and depression and anxiety disorders, 100 whereas multisite CP was found to be a causative for major depressive disorder 63 and far sightedness. 94 By contrast, Mendelian Randomisation found no evidence for a causal effect of alcohol with CWP, 8 obesity with frozen shoulder, 53 or daytime sleepiness with lower back pain. 103 …”

Section: Uk Biobank (Chronic Pain Cohort)mentioning

confidence: 96%

“…The use of both opiate and NeuP pain medications with cardiometabolic medications was associated with obesity, increased waist circumference, and hypertension compared with taking cardiometabolic medications alone and the use of the antidiabetic drug metformin seemed to be protective of musculoskeletal pain. 27 Common opioid (codeine and tramadol), nonsteroidal anti-inflammatory drug (NSAID) (ibuprofen), and NeuP medications were associated with far sightedness 94 and people taking NSAIDs to treat back pain were more likely to report pain persistence than were those not treated with NSAIDs. 92 Studies have also explored pain as a potential exposure for other clinical traits, particularly in longitudinal studies where the outcome has been measured at multiple time points.…”

Section: Outputsmentioning

confidence: 99%

Big data, big consortia, and pain: UK Biobank, PAINSTORM, and DOLORisk

Hébert

Pascal

Smith

et al. 2023

PR9

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Chronic pain (CP) is a common and often debilitating disorder that has major social and economic impacts. A subset of patients develop CP that significantly interferes with their activities of daily living and requires a high level of healthcare support. The challenge for treating physicians is in preventing the onset of refractory CP or effectively managing existing pain. To be able to do this, it is necessary to understand the risk factors, both genetic and environmental, for the onset of CP and response to treatment, as well as the pathogenesis of the disorder, which is highly heterogenous. However, studies of CP, particularly pain with neuropathic characteristics, have been hindered by a lack of consensus on phenotyping and data collection, making comparisons difficult. Furthermore, existing cohorts have suffered from small sample sizes meaning that analyses, especially genome-wide association studies, are insufficiently powered. The key to overcoming these issues is through the creation of large consortia such as DOLORisk and PAINSTORM and biorepositories, such as UK Biobank, where a common approach can be taken to CP phenotyping, which allows harmonisation across different cohorts and in turn increased study power. This review describes the approach that was used for studying neuropathic pain in DOLORisk and how this has informed current projects such as PAINSTORM, the rephenotyping of UK Biobank, and other endeavours. Moreover, an overview is provided of the outputs from these studies and the lessons learnt for future projects.

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Association Between Medication-Taking and Refractive Error in a Large General Population-Based Cohort

Cited by 5 publications

References 51 publications

Mendelian randomization analyses in ocular disease: a powerful approach to causal inference with human genetic data

Mendelian randomization analyses in ocular disease: a powerful approach to causal inference with human genetic data

Association Between Myopic Refractive Error and Primary Open-Angle Glaucoma

Big data, big consortia, and pain: UK Biobank, PAINSTORM, and DOLORisk

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